The present invention provides novel PSMA targeting urea-based ligands that binds to prostate-specific membrane antigen (PSMA) which is expressed 8-to-12-fold higher in prostate cancer cells when compared to healthy tissue. The PSMA targeting urea-based ligands comprises a chelating agent that may comprise a metal and a halogen radioisotope of fluorine, iodine, bromine or astatine. The invention further relates to a method for providing the PSMA targeting urea-based ligands of the invention, to precursors of the PSMA targeting urea-based ligands and to the PSMA targeting urea-based ligands use in radiotherapy, imaging and theranostic.

The present technology is directed to compounds, compositions, medicaments, and methods related to the treatment of cancers expressing PSMA. The compounds are of Formulas I & II

##STR00001##

or pharmaceutically acceptable salts thereof. The present technology is especially well-suited for use in treating prostate cancer.

Conjugates derived from non-steroidal anti-inflammatory drugs (NSAIDs) and methods of use thereof are disclosed, useful for, inter alia, identifying and localizing the site of pathology and/or inflammation responsible for the sensation of pain in a patient; for identifying the sites of primary, secondary, benign, or malignant tumors; and for diagnosing infection or confirming or ruling out suspected infection. The NSAID-based conjugates contain an imaging moiety. The conjugates concentrate at sites of increased cyclooxygenase expression, thus revealing the sites of increased prostaglandin production, which is correlated with pain and inflammation, and correlated with tumor presence and/or location. Identifying areas of increased COX expressing can also aid in screening for infections.

A compound having a structure represented by the general formula (I): ##STR00001##
(wherein n is 0 or 1;
R.sup.1 represents a hydrogen atom (only if n=0), a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, an optionally substituted amino group, an optionally substituted phenyl group, a C1-C6 alkylthio group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group or a C7-C12 aralkyloxy group;
R.sup.2 represents —(CH.sub.2).sub.p—[O(CH.sub.2).sub.q].sub.r—X (wherein X is a halogen atom, p is an integer of 1 to 6, q is an integer of 1 to 4, and r is an integer of 0 to 4);
R.sup.3 represents a hydrogen atom, a C1-C6 alkyl group, a C7-C16 aralkyl group or a C6-C14 aryl group; and
R.sup.4 represents a hydrogen atom or a C1-C6 alkyl group), or a pharmaceutically acceptable salt thereof excels FAMT in terms of the tendency to accumulate intensively in cancer, the affinity for LAT1 and the selectivity for cancer, and can be labeled using an automated synthesizer in clinical settings, and therefore is useful as a highly versatile PET imaging agent.

A visualizable radioactive carbon microsphere (CMS) suspension, a preparation method, and a use thereof are provided. Every 1 mL of the visualizable radioactive CMS suspension includes: CMS: 10 mg to 500 mg; a therapeutic radionuclide with an activity of 5 mCi to 500 mCi; an imaging radionuclide with an activity of 0.1 mCi to 100 mCi; a small organic molecule: 0 mg to 100 mg; and a first solution: 0.1 mL to 1.0 mL. The preparation method mainly includes a process of allowing the CMS to adsorb the small organic molecule, the therapeutic radionuclide, and the imaging zirconium [.sup.89Zr]. The visualizable radioactive CMS suspension can realize both local radiotherapy and real-time imaging of a solid tumor lesion, and thus achieves the visualized treatment of a tumor, which provides a new radioactive CMS product that integrates diagnosis and treatment.

The present invention relates to a ligand-SIF A-chelator conjugate, comprising, within in a single molecule three separate moieties: (a) one or more ligands which are capable of binding to a disease-relevant target molecule, (b) a silicon-fluoride acceptor (SIFA) moiety which comprises a covalent bond between a silicon atom and a fluorine atom, and (c) one or more chelating groups, optionally containing a chelated nonradioactive or radioactive cation.

Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical composition containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.

Lung volume reduction by isolating a target lung portion from the rest of the lung with a mass of extracellular matrix (“ECM”) material. The procedure can be performed by locating a tube within the lumen of an airway to be obstructed and depositing an amount of flowable or other ECM in the open space until the lumen is occluded. Optionally, the procedure may be performed by delivering a plug substantially comprised of ECM material into the lumen of an airway to be obstructed. Further optionally, the ECM plug may include a one-way valve to allow air and mucous to escape from the isolated lung portion.

Carbamate and beta-amino acid urea-based scaffolds that have high binding affinity to PSMA are disclosed. These scaffolds can be radiolabeled and used for imaging cells and tumors that express PSMA or for cancer radiotherapy. These compounds also can comprise a fluorescent dye and be used for imaging cells and tumors that express PSMA or for photodynamic therapy.

Theranostic agents incorporating a chelating moiety that can chelate a radioactive metal isotope and a PSMA-targeting moiety are disclosed herein. The theranostic agents, which can be used to treat and/or detect cancers associated with increased PSMA expression, have the formula:

##STR00001##

and include complexes, anions or salts thereof. Ri includes a chelating moiety; a is 0 or 1; n is an integer from 12 to 21; and R.sub.2 includes a prostate specific membrane antigen (PSMA)-targeting moiety. Optionally, the chelating moiety is chelated to a metal atom, where the metal atom is a positron or single photon emitting metal isotope, or an alpha, beta, or Auger emitting metal isotope.